A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients.

This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the 75selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn's disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (µmol/g) and interquartile ranges in patients in the control group (2.8; 1.6-4.2), BAD (3.6; 1.9-7.2) and post-cholecystectomy cohort 3.8 (2.3-6.8) were similar, but all were significantly lower (p < 0.001) compared to the Crohn's disease cohort (11.8; 10.1-16.2). FBA concentrations in patients with SeHCAT retention of < 15% (4.95; 2.6-10.5) and < 5% (9.9; 4.8-15.4) were significantly higher than those with a SeHCAT retention > 15% (2.6; 1.6-4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 µmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn's patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.

Variation of enterohepatic circulation observed with 75SeHCAT images in the first three hours. Scintigraphic patterns and analysis of their association with the diagnosis of bile acid malabsorption.

OBJETIVE: To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 h and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). MATERIALS AND METHODS: 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1-3 h determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2-3 h, 2) gallbladder 3 h, 3) gallbladder-abdomen 2-3 h, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7 > 15%), mild-BAM (AR7 15-10%), moderate-BAM (AR7 10-5%) or severe-BAM (AR7 < 5%). RESULTS: 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern "gallbladder at 2-3 h" was statistically associated with Non BAM (p 0,008), while "gallbladder-abdomen at 2-3 h" was correlated with having BAM (p 0,029). CONCLUSION: Variations detected at the abdominal level in images during the first 3 h were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

Error analysis of collimated and uncollimated SeHCAT retention measurement using a gamma camera.

AIM: There is increasing interest in using collimated gamma cameras for [75Se]tauroselcholic acid (SeHCAT) studies to image the distribution and to make use of the collimator pressure sensitive devices (PSD) for patient safety. However, the use of a collimator will substantially decrease the sensitivity of the gamma camera. The aim of this article is to enable departments to calculate the uncertainty of SeHCAT retention measurements so that the acquisition time can be optimised to perform a reliable SeHCAT study. METHOD: We derive a mathematical equation from the first principles that can be used to calculate the uncertainty in SeHCAT retention measurements on the basis of Poisson counting statistics. The equation takes account of background subtraction, use of the geometric mean for anterior/posterior attenuation compensation and the day 7 to day 0 quotient calculation. RESULTS: Uncertainties in SeHCAT retention measurement using an intrinsic (uncollimated) gamma camera counting for 100 s are very low, typically of the order 15 ± 0.1%. Uncertainties from collimated gamma camera counting significantly increase for the same 100 s counting duration: 15 ± 0.8% for slim patients and 15 ± 4% for obese patients. CONCLUSION: The acquisition time must be increased for collimated gamma camera SeHCAT counting to achieve acceptable counting statistics for an acceptable total uncertainty in the SeHCAT retention measurement. For slim patients, a minimum counting time of 2 min is required. For larger patients, the acquisition time needs to be increased to 30 min and further increased to 50 min for obese patients.

Bile acid diarrhoea: Current and potential methods of diagnosis.

Chronic diarrhoea is common and mostly due to diarrhoea predominant irritable bowel syndrome. Diarrhoea predominant irritable bowel syndrome affects about 11% of the population; however, up to a third of these patients actually have bile acid diarrhoea. There are, therefore, more than one million sufferers of bile acid diarrhoea in the UK. Bile acid diarrhoea is caused by small bowel malabsorption of bile acids and the increased bile acids in the large intestine cause diarrhoea. Once diagnosed, the treatment of bile acid diarrhoea is simple and effective. Bile acid diarrhoea , however, is often not diagnosed because of a lack of easily available and reliable diagnostic methods. In the United Kingdom, the radiolabelled 23-seleno-25-homotaurocholic acid test is the gold-standard method of diagnosis. 23-seleno-25-homotaurocholic acid test, however, is expensive, inconvenient to the patient, involves radiation exposure and has limited availability. As such, a laboratory biomarker is desirable. This review briefly discusses the pathophysiology and management of bile acid diarrhoea and critically evaluates methods for its diagnosis, including serum 7α-hydroxy-4-cholesten-3-one, faecal bile acid measurement, serum fibroblast growth factor 19, urine-2-propanol, and the 14C-glycocholate breath and stool test.

The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling.

Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-ß-muricholic acid (TßMCA) in the intestine. TßMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TßMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.

The Role of Bile Acids in Chronic Diarrhea.

Bile acids (BAs) are the central signals in enterohepatic communication, and they also integrate microbiota-derived signals into enterohepatic signaling. The tissue distribution and signaling pathways activated by BAs through natural receptors, farsenoid X receptor and G protein-coupled BA receptor 1 (GPBAR1, also known as Takeda G-coupled receptor 5), have led to a greater understanding of the mechanisms and potential therapeutic agents. BA diarrhea is most commonly encountered in ileal resection or disease, in idiopathic disorders (with presentation similar to functional diarrhea or irritable bowel syndrome with diarrhea), and in association with malabsorption such as chronic pancreatitis or celiac disease. Diagnosis of BA diarrhea is based on Se-homocholic acid taurine retention, 48-hour fecal BA excretion, or serum 7αC4; the latter being a marker of hepatic BA synthesis. BA diarrhea tends to be associated with higher body mass index, increased stool weight and stool fat, and acceleration of colonic transit. Biochemical markers of increased BA synthesis or excretion are available through reference laboratories. Current treatment of BA diarrhea is based on BA sequestrants, and, in the future, it is anticipated that farsenoid X receptor agonists may also be effective. The optimal conditions for an empiric trial with BA sequestrants as a diagnostic test are still unclear. However, such therapeutic trials are widely used in clinical practice. Some national guidelines recommend definitive diagnosis of BA diarrhea over empirical trial.

Whole-body 75SeHCAT retention is determined by entero-hepatic bile acid recycling rate.

AIM: It has previously been proposed that entero-hepatic bile acid recycling frequency is a major determinant of whole-body retention (WBR) of SeHCAT. Hepatocyte to terminal ileum accounts for almost the entire cycle. The study aim was to test this hypothesis by comparing WBR with an estimate of speed of transit of bile acids using Tc-HIDA scintigraphy performed on a separate occasion. METHODS: Using an un-collimated gamma camera and patient-to-camera distance of 1.5 m, WBR at 7 days after oral SeHCAT administration was measured in 14 patients with chronic diarrhoea, of whom 10 had previous cholecystectomy. The distance reached within the intestine of Tc-HIDA at 1 h (n = 14) and 2 h (n = 7) following iv injection was graded as follows: grades 1 and 2: small bowel on left and right sides of abdomen, respectively; and grade 3: colon. Relationships between WBR and grade were assessed using Spearman rank correlation. RESULTS: Interval between studies ranged from 3 to 1219 (median 330) days. Grading correlated with WBR at 1 h (rs = -0.63; P = 0.02) and weakly at 2 h (rs = -0.68; P = 0.09) post-injection of Tc-HIDA. In nine patients in whom Tc-HIDA and SeHCAT scans were performed within 1 year of each other, the correlation remained significant at 1 h (rs = -0.73; P = 0.03). There was no difference in WBR or grading between patients with or without a gall bladder. CONCLUSION: Entero-hepatic bile acid recycling frequency is a major determinant of whole-body SeHCAT retention.

Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a heterogeneous disorder, but diagnoses and determination of subtypes are made based on symptoms. We profiled the fecal microbiomes of patients with and without IBS to identify biomarkers of this disorder. METHODS: We collected fecal and urine samples from 80 patients with IBS (Rome IV criteria; 16-70 years old) and 65 matched individuals without IBS (control individuals), along with anthropometric, medical, and dietary information. Shotgun and 16S ribosomal RNA amplicon sequencing were performed on feces, whereas urine and fecal metabolites were analyzed by gas chromatography and liquid chromatography-mass spectrometry. Co-occurrence networks were generated based on significant Spearman correlations between data. Bile acid malabsorption (BAM) was identified in patients with diarrhea by retention of radiolabeled selenium-75 homocholic acid taurine. RESULTS: Patients with IBS had significant differences in network connections between diet and fecal microbiomes compared with control individuals; these were accompanied by differences in fecal metabolomes. We did not find significant differences in fecal microbiota composition among patients with different IBS symptom subtypes. Fecal metabolome profiles could discriminate patients with IBS from control individuals. Urine metabolomes also differed significantly between patients with IBS and control individuals, but most discriminatory metabolites were related to diet or medications. Fecal metabolomes, but not microbiomes, could distinguish patients with IBS with vs those without BAM. CONCLUSIONS: Despite the heterogeneity of IBS, patients have significant differences in urine and fecal metabolomes and fecal microbiome vs control individuals, independent of symptom-based subtypes of IBS. Fecal metabolome analysis can be used to distinguish patients with IBS with vs those without BAM. These findings might be used for developing microbe-based treatments for these disorders.

Methods for diagnosing bile acid malabsorption: a systematic review.

BACKGROUND: Bile acid malabsorption (BAM) and bile acid-related diarrhea represent an under-recognized cause of chronic diarrhea mainly because of limited guidance on appropriate diagnostic and laboratory tests. We aimed to perform a systematic review of the literature in order to identify and compare the diagnostic accuracy of different diagnostic methods for patients with BAM, despite a proven gold standard test is still lacking. METHODS: A PubMed literature review and a manual search were carried out. Relevant full papers, evaluating the diagnostic accuracy of different methods for BAM, were assessed. Available data were analyzed to estimate the sensitivity and specificity of each published test. RESULTS: Overall, more than one test was considered in published papers on BAM. The search strategy retrieved 574 articles; of these, only 16 were full papers (with a total of 2.332 patients) included in the final review. Specifically, n = 8 studies used 75Selenium-homotaurocholic-acid-test (75SeHCAT) with a < 10% retention threshold; n = 8 studies evaluated fasting serum 7-α-hydroxy-4-cholesten-3-one (C4); n = 3 studies involved total fecal bile acid (BA) excretion over 48 h; n = 4 studies assessed fibroblast growth factor 19 (FGF19). 75SeHCAT showed an average sensitivity and specificity of 87.32 and 93.2%, respectively, followed by serum C4 (85.2 and 71.1%) and total fecal BA (66.6 and 79.3%). Fasting serum FGF19 had the lowest sensitivity and specificity (63.8 and 72.3%). All the extracted data were associated with substantial heterogeneity. CONCLUSIONS: Our systematic review indicates that 75SeHCAT has the highest diagnostic accuracy for BAM, followed by serum C4 assay. The diagnostic yield of fecal BA and FGF19 assays is still under investigation. Our review reinforces the need for novel biomarkers aimed to an objective detection of BAM and therefore improving the management of this condition.

Capsaicin Improves Glucose Tolerance and Insulin Sensitivity Through Modulation of the Gut Microbiota-Bile Acid-FXR Axis in Type 2 Diabetic db/db Mice.

SCOPE: Previous studies have linked dietary capsaicin (CAP) intake to improved glucose homeostasis and insulin sensitivity. However, the underlying mechanisms remain unclear. METHODS AND RESULTS: Type 2 diabetic db/db mice are fed a chow diet with or without CAP treatment for 8 weeks. CAP administration markedly improves glucose tolerance and insulin sensitivity through decreasing gluconeogenesis and increasing glycogen synthesis in the liver. Furthermore, CAP inhibits the increase in abundance of the genus Lactobacillus and its bile salt hydrolase (BSH) activity compared with levels in chow-fed mice, thereby leading to the accumulation of tauro-ß-muricholic acid (TßMCA), a natural antagonist of the farnesoid X receptor (FXR) that is involved in the regulation of BA and glucose metabolism. CAP-induced suppression of enterohepatic FXR-fibroblast growth factor 15 (FGF15) signaling contributes to the increased BA pool size, followed by increases in the expression of cholesterol 7α-hydroxylase (CYP7A1) and hepatic BA synthesis. Additionally, depleting gut microbiota by antibiotics administration abolishes the beneficial effects of CAP on BA metabolism and glucose homeostasis. CONCLUSIONS: CAP-induced improvements in BA and glucose metabolism are partially mediated by the gut microbiota-BA-enterohepatic FXR axis in db/db mice.

Prevalence of, and predictors of, bile acid diarrhea in outpatients with chronic diarrhea: A follow-up study.

BACKGROUND: 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning to rule out bile acid diarrhea (BAD) in patients with chronic diarrhea has a high yield. Our previous study showed that patients with terminal ileal (TI) Crohn's disease, TI resection, or cholecystectomy were highly likely to have an abnormal scan. As a result, we encouraged clinicians to use a therapeutic trial of a bile acid sequestrant in these patients, instead of scanning. This may have reduced diagnostic yield of the test, so we examined this issue, as well as factors predicting an abnormal scan, in a large cohort of patients referred subsequently. METHODS: We retrospectively identified 1,071 consecutive patients with chronic diarrhea undergoing SeHCAT scanning at Leeds Teaching Hospitals Trust from 2012 to 2016. We reviewed electronic patient records to obtain information on presenting gastrointestinal symptoms and any proposed risk factors for BAD. BAD was categorized according to subtype and severity. KEY RESULTS: As expected, indications for scanning changed between 2012 and 2016, with a significant reduction in referrals with TI Crohn's disease or resection year-on-year (P < 0.001). Despite this, 457 (42.7%) patients had BAD and there was no downward trend in yield of SeHCAT during the 5 year period (P = 0.39). Overall, 51.6% had type II BAD, 36.1% type III, and 12.3% type I. BAD was mild in 31.7%, moderate in 34.4%, and severe in 33.9%. In total, 653 (61.0%) patients had no known risk factors, other than chronic diarrhea, but 233 (35.7%) of these individuals had BAD, and in 143 (61.4%), this was moderate or severe. CONCLUSIONS AND INFERENCES: Despite reduced referrals for SeHCAT scanning in those with clear risk factors for BAD, the yield remained > 40%. One-third of those without known risk factors had BAD.

[Primary bile acid diarrhea in a community gastroenterology practice]. / Die primäre chologene Diarrhö in einer gastroenterologischen Praxis.

When first described in 1976, primary bile acid diarrhea (BAD Type 1) was regarded as a very rare cause of chronic diarrhea. Today, the incidence is estimated as > 1 %. Availability of diagnostic tools varies widely and, in Germany, there is no generally consented recommendation for their use. BAD is still widely underdiagnosed.Since the beginning of the '90 s, we have added a therapeutic trial with cholestyramine to our diagnostic approach of chronic diarrhea. Patients with a positive test were offered a Selenium-homocholic acid taurine (SeHCAT) test for confirmation of bile-acid-diarrhea (BAD), using a 7-day-retention of 20 % as cut-off value.From April 1991 to March 2017, after exclusion of other relevant causes for chronic diarrhea like IBD, celiac disease or microscopic colitis, 70 patients with a positive trial treatment of cholestyramine were identified for evaluation. Sixty of them had a SeHCAT test. Patients with BAD Type 1 and Type 3 were excluded, except for cholecystectomy.85 % (35/41) of patients with BAD Type 1 needed continued medical treatment (median follow-up time 8.3 (1 - 23.6) years). Among them, 68.6 % (24/35) took cholestyramine, 31.4 % (11/35) loperamide or another antidiarrheal treatment. 14.6 % (6/41) of patients reported a spontaneous remission after median 2.9 (0.7 - 5.7) years.In the group of patients with BAD after cholecystectomy, 82 % (8/11) still needed treatment after median 7.7 (1 - 24.5) years; 8 having taken cholestyramine, one patient nothing and two with spontaneous remissions.All (8/8) patients with a normal SeHCAT test (7-day retention > 20 %) had spontaneous relief after median 3.6 (1.2 - 6.3) months.Also, 70 % (7/10) of patients who had not been confirmed by the SeHCAT test still needed treatment after median 4.3 (3.7 - 18.3) years.Based on a trial treatment alone, diagnosis of BAD is possible but not assured. Due to its ubiquitous availability, it should be used consequently if other methods are not available. Despite the well-known shortcomings of cholestyramine, a therapeutic trial should be used more consequently. According to the current literature, using the SeHCAT test in the first place will give significantly better results and unnecessary follow-up examinations can be avoided. However, therapeutic consequences might be modest due to the well-known limitations of cholestyramine. A well-tolerated and licensed alternative to cholestyramine is urgently needed.

75Se-Homocholic acid taurine scintigraphy (75SeHCAT®), a standard benchmark test in bile acid malabsorption? / Gammagrafía con 75Se-ácido tauroselcólico (75SeHCAT®), ¿prueba de referencia en la malabsorción de ácidos biliares?

Chronic diarrhoea due to bile acid malabsorption (BAM) is an underdiagnosed pathology. Different diagnostic tools are available. However, there is currently no consensus on which of these would be the benchmark test or gold standard. This review evaluates the possibility of using 75Se-taurocholic acid (75SeHCAT®) scintigraphy as a benchmark diagnostic test and its perspective for the future. A literature review was conducted in Pubmed and OVID obtaining a total of 57 papers, 26 of which were finally used after being selected under the concepts of gold standard, diagnostic accuracy and other biomarkers. We evaluated the advantages and disadvantages of the different diagnostic tools: 14C-glycocholate, measurement of bile acids in faeces, C4 in serum, FGF19 in serum, cholestyramine, and 75Se-tauroselcolic acid scintigraphy. We consider that the 75SeHCAT® scan is the most recommended diagnostic test in Europe for diagnosing BAM as it presents the highest values of sensitivity and specificity. It has a significant cost-benefit ratio, making it the test with the highest degree of recommendation. However, it is still not possible to use it in a recognised way as a gold standard due to the lack of studies that provide conclusive data that allow consensus. In the meantime, the combined use of cholestyramine testing in all patients we want to evaluate, regardless of the scintigraphy result, could be encouraged as a benchmark standard.

FXR Regulates Intestinal Cancer Stem Cell Proliferation.

Increased levels of intestinal bile acids (BAs) are a risk factor for colorectal cancer (CRC). Here, we show that the convergence of dietary factors (high-fat diet) and dysregulated WNT signaling (APC mutation) alters BA profiles to drive malignant transformations in Lgr5-expressing (Lgr5+) cancer stem cells and promote an adenoma-to-adenocarcinoma progression. Mechanistically, we show that BAs that antagonize intestinal farnesoid X receptor (FXR) function, including tauro-ß-muricholic acid (T-ßMCA) and deoxycholic acid (DCA), induce proliferation and DNA damage in Lgr5+ cells. Conversely, selective activation of intestinal FXR can restrict abnormal Lgr5+ cell growth and curtail CRC progression. This unexpected role for FXR in coordinating intestinal self-renewal with BA levels implicates FXR as a potential therapeutic target for CRC.

Systematic review with meta-analysis: the prevalence of bile acid malabsorption and response to colestyramine in patients with chronic watery diarrhoea and previous cholecystectomy.

BACKGROUND: A limited number of small-sized studies suggest that bile acid diarrhoea is frequent in patients with chronic watery diarrhoea and previous cholecystectomy. AIM: To perform a systematic review and meta-analysis to assess the prevalence of bile acid diarrhoea in patients with chronic watery diarrhoea and previous cholecystectomy, and their response to colestyramine, including a new consecutive series of patients. METHODS: MEDLINE and EMBASE were searched up to January 2018. Selected studies included patients with previous cholecystectomy and chronic watery diarrhoea assessed by the 23-seleno-25-homotaurocholic acid (SeHCAT) test. We calculated the pooled rate of bile acid diarrhoea using the inverse double arcsine square root method. Additionally, the medical records of 291 consecutive patients with chronic watery diarrhoea in whom a SeHCAT test was performed were retrospectively reviewed and 74 with previous cholecystectomy were included in the meta-analysis. RESULTS: The search strategy identified eight relevant studies, which, together with the data of the present series, comprise 361 individuals. The pooled bile acid diarrhoea rate was 70% (95% CI 56%-82%), and was similar when using cut-offs of 10% or 15%. There was substantial heterogeneity (I2  = 84%). Five studies comprising 166 patients evaluated the effect of colestyramine in patients with bile acid diarrhoea. The pooled colestyramine response rate was 79% (95% CI 63%-91%) with substantial heterogeneity (I2  = 73%). CONCLUSIONS: Two-thirds of patients with chronic watery diarrhoea and previous cholecystectomy have bile acid diarrhoea. Response to colestyramine in these patients is good.

Administration of antibiotics contributes to cholestasis in pediatric patients with intestinal failure via the alteration of FXR signaling.

The link between antibiotic treatment and IF-associated liver disease (IFALD) is unclear. Here, we study the effect of antibiotic treatment on bile acid (BA) metabolism and investigate the involved mechanisms. The results showed that pediatric IF patients with cholestasis had a significantly lower abundance of BA-biotransforming bacteria than patients without cholestasis. In addition, the BA composition was altered in the serum, feces, and liver of pediatric IF patients with cholestasis, as reflected by the increased proportion of primary BAs. In the ileum, farnesoid X receptor (FXR) expression was reduced in patients with cholestasis. Correspondingly, the serum FGF19 levels decreased significantly in patients with cholestasis. In the liver, the expression of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1), increased noticeably in IF patients with cholestasis. In mice, we showed that oral antibiotics (gentamicin, GM or vancomycin, VCM) reduced colonic microbial diversity, with a decrease in both Gram-negative bacteria (GM affected Eubacterium and Bacteroides) and Gram-positive bacteria (VCM affected Clostridium, Bifidobacterium and Lactobacillus). Concomitantly, treatment with GM or VCM decreased secondary BAs in the colonic contents, with a simultaneous increase in primary BAs in plasma. Moreover, the changes in the colonic BA profile especially that of tauro-beta-muricholic acid (TßMCA), were predominantly associated with the inhibition of the FXR and further altered BA synthesis and transport. In conclusion, the administration of antibiotics significantly decreased the intestinal microbiota diversity and subsequently altered the BA composition. The alterations in BA composition contributed to cholestasis in IF patients by regulating FXR signaling.